Tumor cells display enhanced sensitivity to disruptions in the ubiquitin-proteasome system (UPS) making this an attractive target for the development of anti-cancer therapies (1). Ubiquitin-tagged substrates are recognized for destruction by the 26S proteasome; a multi-subunit complex comprising a proteolytic 20S core (20S CP) capped by 19S regulatory particles (19S RP) (2,3). The 20S CP has evolved as an important target for anti-cancer drug development, resulting in the approval of bortezomib (Velcade®) for treatment of myeloic leukemia (4). The low molecular weight compound b-AP15 (NSC687852) is known to induce p53-independent and cathepsin-D-dependent apoptosis (5,6).